The present invention relates to a class of aryl ether derivatives useful as herbicides and desiccants.
Various substituted phenyl ethers (Ixe2x80x2) are known in literature. Q may be uracil, triazine, pyridazine, pyrazole, etc., R may be hydrogen, alkyl, cycloalkyl, alkenyl, or alkynyl. WO 98/41093 and U.S. Pat. No. 6,121,201 describe certain diaryl ethers as herbicides. WO 00/50409 describes herbicidal compounds containing 1-aryl-1,3,5-triazine-4-thione-2,6-dione derivatives. WO 99/14201 describes certain 2-phenyl-3(2H)-pyridazinone derivatives and WO 99/59983 describes certain 6-aryl-3,5-dithioxo-2,3,4,5-tetrahydro-1,2,4-triazine and 6-aryl-3-thioxo-5-oxo-2,3,4,5-tetrahydro-1,2,4-triazine derivatives as herbicides. WO 96/15115 and WO 00/12480 describes a group of substituted phenyl pyrazole derivatives as herbicides. WO 93/15074 and U.S. Pat. No. 5,670,455 describe certain aryl substituted fused pyrazole derivatives as herbicides. 
WO96/07323 and WO96/08151 disclose some known uracil compounds. In WO96/07323 and WO96/08151, the generic representation is significantly broader than the disclosures set forth in them, and in the prior art patents.
However the specific aryl ether compounds of the formula (I) mentioned below are not known and are novel. Furthermore the present invention reveals that the aryl ether derivatives represented by the general formula (I) or their salts have potent herbicidal activity and/or desiccant activity with good crop safety.
This invention relates to aryl ether derivatives represented by the following general formula (I) and their salts: 
wherein X and Y are independent of each other and are represented by hydrogen, halogen, cyano, nitro, (C1-4)alkyl, (C1-4)haloalkyl, or (C1-4)haloalkoxy;
Z is oxygen or sulfur;
Q is 
xe2x80x83A is oxygen, sulfur, or imino;
R1 is hydrogen, (C1-4)alkyl, or (C1-4)haloalkyl, and can be independent of each other;
R2 and R3 are independent of each other and may be selected from the group consisting of hydrogen, halogen, cyano, nitro, (C1-4)alkyl, (C1-4)haloalkyl, (C2-6)alkenyl, (C2-6)haloalkenyl and amino which may be optionally substituted with (C1-4)alkyl or (C1-4)haloalkyl;
Ar is substituted or unsubstituted carbocyclic or heterocyclic aromatic ring being at least a five or six membered ring. This ring can be fused with another substituted or unsubstituted five or six membered carbocyclic or heterocyclic ring; when Q is Q5, unsubstituted or substituted phenyl is excluded.
This invention also relates to herbicidal and/or desiccant compositions containing them, and to methods for using these compositions. Further this invention sometimes relates to methods for the control of undesired vegetation in a plantation crop by the application to the locus of the crop an effective amount of the compounds described herein, as broad spectrum herbicides which are effective against a variety of weed species in pre emergence and post emergence applications with crop safety. Furthermore this invention relates to methods for preparing these compounds and intermediates thereof
The present invention provides the aryl ether compounds having the general formula (I) and salts thereof 
wherein X, Y, Z, Ar, and Q are as described above.
The aryl in the definition of Ar may be a substituted or unsubstituted carbocyclic or heterocyclic aromatic ring being at least a five or six membered ring. This ring can be fused with another substituted or unsubstituted five or six membered carbocyclic or heterocyclic aromatic ring. For example, the carbocyclic aromatic ring in the definition of Ar may be aryl such as phenyl or naphthyl, and the heterocyclic aromatic ring in the definition of Ar may be a five or six membered ring having at least one heterogeneous atom of nitrogen, oxygen or sulfur, and for example may be pyridyl, pyrimidyl, pyridazinyl, triazolyl, thiazolyl, isothiazolyl, quinoline, or isoquinoline. The substituents for the substituted carbocyclic or heterocyclic aromatic ring in the definition of Ar may, for example, be halogen, (C1-6)alkyl, halo(C1-6)alkyl, (C1-6)alkoxy, halo(C1-4))alkoxy, (C1-6)alkylthio, (C1-6)alkylsulfonyl, (C1-6)alkylsulfinyl, (C1-6)dialkylaminocarbonyl, cyano, nitro, amino, hydroxy, (C1-6)alkylsulfonylamino, (C1-6)alkoxycarbonyl(C1-6)alkoxy, (C1-6)alkoxycarbonyl-halo(C16)alkyl, (C2-6)alkenyloxycarbonyl(C1-6)alkoxy(C1-6)alkyl, (C1-6)alkylcarbonylamino, bisbenzoylamino, aminoacetyl, aminotrifluoroacetyl, or amino(C1-6)allylsulfonate. The number of substituents therefor is one or more, for example up to seven. When the number is two or more, the substituents may be same or different. When Q is Q5, unsubstituted or substituted phenyl is excluded.
Some compounds of formula (I) and their intermediates may occasionally exist as geometrical or optical isomers and the present invention includes all of these isomeric forms. Some compounds of the formula (I) and their intermediates may form a salt with an acidic substance or a basic substance. The salt with an acidic substance may be an inorganic acid salt such as a hydrochloride, a hydrobromide, a phosphate, a sulfate or a nitrate. The salt with a basic substance may be a salt of an inorganic or organic base such as a sodium salt, a potassium salt, a calcium salt, a quaternary ammonium salt such as ammonium salt or a dimethylamine salt.
The alkyl group and alkyl part in the definition related to X, Y, R1 to R3 and the substituents for the substituted aryl and heteroaryl ring as Ar have straight or branched chains with C1-6, preferably C1-4 such as methyl, ethyl, propyl, butyl, pentyl, or hexyl. The alkenyl group and their parts in the definition for R2 and R3 have also straight or branched chains with C2-6, preferably C2-4 such as vinyl, propenyl, butenyl, pentenyl or hexenyl.
The halogen atom and halogeno part in the definition related to X, Y, and R1 to R3 are fluorine, chlorine, bromine, or iodine. The haloalkyl or haloalkenyl group constitutes the alkyl or alkenyl group and one or more halogen atoms as mentioned above. When the number of halogen atom is two or more, halogen atoms may be same or different.
Preferred formula (I) compounds of this invention are those wherein
X, and Y are independently hydrogen, or halogen;
Z is oxygen or sulfur;
Q is selected from Q1, Q2, Q5, or Q6
Ar is pyridyl, pyrimidyl, triazolyl, thiazolyl, isothiazolyl, or phenyl; or each of pyridyl, pyrimidyl, triazolyl, thiazolyl, isothiazolyl, or phenyl being substituted with up to five substituents independently selected from bromine, chlorine, fluorine, iodine, (C1-C4)alkyl, halo(C1-4)alkyl, (C1-4)alkoxy, (C1-4)alkylthio, halo(C1-4)alkoxy, (C1-C4)alkylsulfonyl, (C1-C3)alkylsulfinyl, di(C1-4)alkylaminocarbonyl, cyano, nitro, amino, hydroxy, (C1-4)alkylsulfonylamino, (C1-4)alkoxycarbonyl(C1-4)alkoxy, or (C1-4)alkoxycarbonylamino. When Q is Q5, unsubstituted or substituted phenyl is excluded.
The most preferred formula (I) compounds of this invention are those wherein
X is fluorine;
Y is chlorine;
Z is oxygen or sulfur;
Q is selected from Q1, Q2, or Q5.
Ar is 2-pyridyl, 3-pyridyl, 4-pyridyl, 3-bromo-2-pyridyl, 5-bromo-2-pyridyl, 6-bromo-2-pyridyl, 3-chloro-2-pyridyl, 5-chloro-2-pyridyl, 6-chloro-2-pyridyl, 3-fluoro-2-pyridyl, 5-fluoro-2-pyridyl, 6-fluoro-2-pyridyl, 3-cyano-2-pyridyl, 5-cyano-2-pyridyl, 6-cyano-2-pyridyl, 3-nitro-2-pyridyl, 5-nitro-2-pyridyl, 6-nitro-2-pyridyl, 3-trifluoromethyl-2-pyridyl, 4-trifluoromethyl-2-pyridyl, 5-trifluoromethyl-2-pyridyl, 6-trifluoromethyl-2-pyridyl, 5-amino-2-pyridyl, 3-dimethylaminocarbonyl-2-pyridyl, 3-methylsulfonyl-2-pyridyl, 3-isopropylsulfonyl-2-pyridyl, 6-chloro-3-trifluoromethyl-2-pyridyl, 3,5,6-trifluoropyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-bromo-2-pyrimidyl, 4-chloro-2-pyrimidyl, 4-trifluoromethyl-2-pyrimidyl, 4,6-dimethoxy-2-pyrimidyl, 2,6-dimethoxy-4-pyrimidyl, 4,6-dimethoxy-2-triazinyl, phenyl, 2-iodophenyl, 2-trifluoromethoxyphenyl, 2-nitrophenyl, 4-nitrophenyl, 4-aminophenyl, 4-hydroxyphenyl, 4-methylsulfonylaminophenyl, 4-(1-ethoxycarbonylethoxy)phenyl, 2-cyanophenyl, 2-cyano-3-fluorophenyl, 2-cyano-4-fluorophenyl, 2-amino-4-(1-ethoxycarbonylethoxy)-phenyl, 2-cyano-4-nitrophenyl, 4-amino-2-cyanophenyl, 4-nitro-2-trifluoromethylphenyl, 4-amino-2-trifluoromethylphenyl, 4-acetylamino-2-trifluoromethylphenyl, 4-(1-ethoxycarbonylethoxy)-2-nitrophenyl, 5-chloro-4-(1-ethoxycarbonylethoxy)-2-nitrophenyl, 3-methyl-4-nitro-5-isothiazolyl, or 5-nitro-2-thiazolyl. When Q is Q5, unsubstituted or substituted phenyl is excluded.
The intermediate (III) can be prepared by the methods mentioned in Process 1. Starting materials (XIV) can be prepared according to the procedures described in the publications e.g. WO 98/41093 and WO 00/32573. The step requires treatment of the amine (XIV) with thiophosgene in a solvent such as hexane, heptane, benzene, toluene, xylene, or ethyl acetate in the presence of a base such as triethylamine, pyridine, lutidine, etc. The reaction temperature is usually from 0xc2x0 C. to the reflux temperature of the mixture, preferably at the reflux temperature of the mixture. The reaction time is usually from 30 minutes to 6 hours, preferably from 2 to 3 hours. Alternatively, the aniline (XIV) can be converted into a salt of a dithiocarbamate by treatment with carbondisulfide in the presence of a base such as triethyl amine, pyridine, ethanolic aqueous ammonia, or sodium hydroxide. The dithiocarbamate can be converted into the isothiocyanate (III) by treatment with reagents such as ferrous sulfate, zinc sulfate, copper sulfate, or lead nitrate. The dithiocarbamate can also be converted into the isothiocyanate (III) by decomposition of a carboethoxy or a carbomethoxy derivative which can be prepared by treatment with ethylchloroformate or methylchloroformate. 
Process 2 is carried out by the reaction of a phenol (II) with an aryl halide or an heteroaryl halide with or without solvents. The solvents may include acetonitrile, tetrahydrofuran, dimethylsulfoxide, hexamethylphosphoric triamide, N,N-dimethylformamide, acetone, butan-2-one, benzene, toluene or xylene, in the presence of a base such as potassium carbonate, sodium carbonate, potassium hydroxide, sodium hydroxide, potassium t-butoxide, potassium fluoride, or sodium hydride. Catalysts may or may not be used. Such catalysts include copper(1)chloride, copper(1)oxide, copper, copper(1)alkoxide, alkyl cuprate, palladium(0), tetrabutylammonium halides, or 8-quinolinol. The reaction temperature is usually from 0xc2x0 C. to 250xc2x0 C., preferably from 20xc2x0 C. to 120xc2x0 C. The reaction time is usually from 1 to 12 hours, preferably from 2 to 6 hours. The aryl ether derivatives (1) may also be prepared by treatment of phenol (II) with aryl-lead tricarboxylates, triphenylbismuth-diacetate, triphenylbismuth-trifluoroacetate or diphenyliodonium halides in the presence of solvents such as benzene, toluene, dichloromethane, dichloroethane, chloroform or water, with or without catalysts such as copper, or a transition metal. The temperature is usually from 0xc2x0 C. to the reflux temperature of the mixture, and the reaction time from 10 minutes to 72 hours. The temperature is preferably from 20xc2x0 C. to the reflux temperature of the mixture, and the time preferably 2 to 6 hours.
The said phenol of formula (II) or its salt may be prepared by a similar process as disclosed in WO 98/41093 etc. or by a reaction of a compound having an alkyl or heteroaryl group except for the Ar group of the compound of the formula (I) with a hydrolytic agent such as borontribromide, lithium chloride, or hydrobromic acid, according to the conventional process.
Alternatively Process 2 may be carried out by the reaction of a halobenzene (XII) with an aryl or heteroaryl hydroxy compound or thiohydroxy compound in the similar reaction conditions. 
Using Process 3, an isothiocyanate (III) may be used to form the thionouracil (XV) by reacting the isothiocyanate (Ill) with an alkyl 3-methylamino-4,4,4-trifluorocrotonate and a base such as sodium hydride, sodium methoxide or sodium ethoxide, in a solvent such as dimethylsulfoxide, N,N-dimethylformamide, benzene, toluene, xylene, tetrahydrofuran, dioxane, or diethyl ether, at temperatures usually from xe2x88x9250xc2x0 C. to 50xc2x0 C., with a reaction time from 10 minutes to 14 hours, preferably between xe2x88x9230xc2x0 C. to 30xc2x0 C., with a reaction time of 15 minutes to 6 hours.
Alternatively Process 3 may be carried out by using a compound of the formula (V) having a radical; xe2x80x94NHC(S)xe2x80x94OR5 (R5; C1-4alkyl or phenyl) except for the isothiocyanate group of the isothiocyanate of the formula (III) in the similar reaction conditions. 
Using Process 4, a compound of formula (IX) can be prepared by reacting a compound of the formula (VIII), such as the above compound of formula (XV), with a thionating agent such as Lawesson""s reagent or phosphorus pentasulfide. Further sulfurization may occur with prolonged heating and with excess reagent. The reaction uses solvents such as benzene, toluene and xylene. The reaction time is usually from 2 to 12 hours, preferably from 3 to 4 hours. The reaction temperature is usually from 0xc2x0 C. to 150xc2x0 C., preferably between 60xc2x0 C. and the reflux temperature of the mixture. 
Process 5 is carried out in two stages. The first step is the formation of the (un)substituted benzyl uracil (XIX) via a compound (XVIII) from the corresponding benzyl amine (XVII) using the methodology described in Processes 1 and 3. The benzyl substituent at the 3 position of the uracil ring is removed by treatment with Lewis acids such as aluminium trichloride, zinc chloride, or ceric ammonium nitrate in organic solvents such as toluene, xylene, chloro benzene, or acetonitrile to provide the uracil(VI). The reaction temperature is usually from 0xc2x0 C. to 200xc2x0 C., preferably from 20xc2x0 C. to the reflux temperature of the mixture. The reaction time is from 1 to 24 hours, preferably from 2 to 12 hours. 
Process 6 shows that the uracil derivatives (XV) may be formed by reacting the prepared uracil (VI) with an aryl ether derivative (VII) carrying a leaving group represented by L. L can be substituents such as an activated halogen, a triflate, a tosyl group, or a nitro group. The reaction is carried out in the presence of an inorganic base such as sodium hydride, potassium carbonate, or an organic base such as triethyl amine, lutidine, or diazabicycloundecene in a solvent such as dimethylsulfoxide, N,N-dimethylformamide, benzene, toluene, xylene, tetrahydrofuran, dioxane, methyl ethyl ketone or diethyl ether, at temperatures usually from xe2x88x9220xc2x0 C. to 160xc2x0 C., with a reaction time from 1 hour to 12 hours, preferably from 0xc2x0 C. to 130xc2x0 C., with a reaction time of 1 hour to 6 hours. 
Process 7 shows that the triazine ring in compound (XX) can be formed by reacting the isocyanate (X) with a thiourea derivative such as 1,3-dimethylthiourea and a carbonylation reagent such as phosgene, diphenylcarbonate, or N,Nxe2x80x2-carbonyldiimidazole. The reaction is carried out in the presence of a base such as triethyl amine, pyridine, or lutidine in a solvent such as N,N-dimethylformamide, toluene, xylene, tetrahydrofuran, dioxane, or methyl ethyl ketone, at temperatures usually from xe2x88x9220xc2x0 C. to 120xc2x0 C., with a reaction time from 1 hour to 24 hours, preferably from 20xc2x0 C. to 80xc2x0 C. with a reaction time of 2 hours to 6 hours. 
Process 8 is carried out in four stages. The first step is the formation of the pyridazone ring system through a condensation of the corresponding phenylhydrazine, (XXI), with mucochloric acid with or without solvents. Examples of solvents for this reaction include methanol, ethanol, toluene, tetrahydrofuran, dioxane, etc. Reaction temperatures range between 40xc2x0 C. to 200xc2x0 C., preferably from 60xc2x0 C. to 100xc2x0 C., and reaction times range between 2 to 48 hours, preferably from 12 to 16 hours.
In the second step, the pyridazone compound, (XXII), is reacted with an inorganic salt of an alkyl mercaptan in an inert solvent such as tetrahydrofuran, 1,4-dioxane, benzene, toluene, N,N-dimethylformamide, or dimethyl sulfoxide to form the compound (XXIII). The reaction temperature is usually from 0xc2x0 C. to 100xc2x0 C., preferably ambient temperature, and a reaction time usually from 10 minutes to 6 hours, preferably 30 minutes to 1 hour.
The sulfone (XXIV) is obtained by oxidation of compound (XXIII) with such oxidizing agents as peroxides or oxone usually in a halogenated solvent such as methylene chloride, chloroform, or carbon tetrachloride. The reaction time is usually from 10 minutes to 6 hours, preferably from 1 to 2 hours, and the reaction temperature is usually from 0xc2x0 C. to 100xc2x0 C., preferably ambient temperature.
The final step is the halogen exchange reaction with nucleophiles leading to the pyridazone compound (XXV). Examples of the nucleophiles include methanolic ammonia, sodamide, ammonia, etc. The solvent is usually an inert solvent such as tetrahydrofuran, 1,4-dioxane, benzene, toluene, xylene, or N,N-dimethylformamide. The reaction temperature is usually between 0xc2x0 C. and 200xc2x0 C., preferably between 40xc2x0 C. to 60xc2x0 C., with a reaction time between 2 to 48 hours, preferably from 2 to 12 hours. 
Process 9 is carried out in three stages. The first step is the formation of compound (XXVI) from the corresponding substituted aniline (XIV, Axe2x95x90NH2) by diazotization of the amine followed by conversion to the halide by treatment with an inorganic halide such as sodium iodide, potassium iodide, sodium bromide, or potassium bromide. The reaction can be carried out in aqueous acids such as hydrochloric acid, sulfuric acid, or acetic acid at temperatures of from xe2x88x9240xc2x0 C. to 80xc2x0 C., preferably from 0xc2x0 C. to 10xc2x0 C., and the reaction time is from 10 minutes to 12 hours, preferably from 0.5 to 2 hours. Alternatively, compound (XXVI) can be prepared by direct halogenation of the corresponding aryl ether (XIV, ASH) with reagents such as chlorine, bromine, N-chlorosuccinimide, N-bromosuccinimide, and N-iodosuccinimide. The reaction can be carried out in organic solvents such as N,N-dimethylformamide, dimethylsulfoxide, chloroform, or dichloromethane at temperatures of from xe2x88x9220xc2x0 C. to 150xc2x0 C., preferably from 10xc2x0 C. to 80xc2x0 C. The reaction time is from 1 to 24 hours, preferably from 2 to 12 hours.
The second step is the formation of the Grignard reagent followed by treatment with an acid halide derived from a monoalkyl ester of oxalic acid. The Grignard reagent is formed with magnesium in an aprotic solvent such as diethyl ether, tetrahydrofuran, dioxane, benzene, toluene, xylene, etc. at temperatures from 0xc2x0 C. to 100xc2x0 C., preferably from 10xc2x0 C. to 60xc2x0 C., with or without catalytic amounts of iodine. Reaction times are usually from 10 minutes to 24 hours, preferably from 0.5 to 2 hours. The Grignard reagent is treated with an acid halide derived from a monoalkyl ester of oxalic acid such as ethyl chlorooxoacetate to form (un)substituted thiosemicarbizides (XXVIII). The reaction time during and after the addition is from 1 to 24 hours, preferably from 2 to 12 hours at temperatures of from xe2x88x92110xc2x0 C. to 100xc2x0 C., preferably from xe2x88x9280xc2x0 C. to 25xc2x0 C.
The third step is the formation of the 1,2,4-triazine (XXVIII) by condensation of (un)substituted thiosemicarbizides (XXVII). The solvent may include protic solvents, such as methanol, ethanol, isopropanol, etc. for a reaction time usually from 2 to 48 hours, preferably from 2 to 12 hours and a reaction temperature of from 0xc2x0 C. to 200xc2x0 C., preferably between 40xc2x0 C. and the reflux temperature of the solvent. 
Process 10 shows that compounds (XXX) can be prepared by oxidizing starting materials such as compounds (XXIX). The reaction is carried out in the presence of an oxidizing agent such as hydrogen peroxide or m-chloroperbenzoic acid in a solvent such as chloroform, toluene, or ether such as diethyl ether, at temperature from xe2x88x9220xc2x0 C. to 250xc2x0 C., with a reaction time from 0.5 to 36 hours, preferably from 20xc2x0 C. to 150xc2x0 C. with a reaction time of 1 to 24 hours. The said compounds (XXIX) or their salts may be prepared by a similar process as disclosed in WO 98/41093 etc. 
The synthesis of compounds (XXXIV) proceeds in 3 stages (a-c) as shown in Process 11. Compounds (XXXI) can be prepared by reaction between compounds (XXVI) and acetylene derivatives such as trimethylsilyl acetylene, in the presence of a metal catalyst such as bis(triphenylphosphine)palladium chloride with a co-catalyst such as copper iodide in a solvent such as toluene, xylene or triethylamine, at temperatures from xe2x88x9220xc2x0 C. to 200xc2x0 C., with a reaction time from 0.5 to 24 hours, preferably from 20xc2x0 C. to 150xc2x0 C. with a reaction time from 1 to 12 hours. The second step is the formation of compounds (XXXIII) from the corresponding compounds (XXXI). The reaction is carried out in the presence of compounds (XXXII) in an inert solvent such as toluene, xylene or biphenyl, at a temperature from 0xc2x0 C. to 300xc2x0 C., preferably from 50xc2x0 C. to 200xc2x0 C. The reaction time is usually from 1 to 72 hours, preferably 2 to 12 hours. The third step is the synthesis of compounds (XXXIV) from the corresponding compounds (XXXIII). The reaction is carried out in the presence of halogenating reagent such as chlorine, N-chlorosuccinimde, bromine or N-bromosuccinimide in a solvent such as N,N-dimethylformamide, at temperature from 0xc2x0 C. to 200xc2x0 C., preferably 20xc2x0 C. to 150xc2x0 C. The reaction time is 0.5 to 24 hours, preferably 1 to 6 hours. 
Process 12 shows that a compound of the formula (I), with Q as Q1, can be prepared by reacting a compound of the formula (VIIIxe2x80x2) (R1 is hydrogen) with an alkylating reagent such as an alkyl halide or haloalkyl halide in the presence or absence of a base, according to the conventional reaction conditions. 